Venous leg ulceration (VLU), the most common type of chronic ulcer, can be difficult to heal and is a major cause of morbidity and reduced quality of life. Although compression bandaging is the principal treatment, it is time-consuming and bandage application requires specific training. There is evidence that intervention on superficial venous incompetence can help ulcer healing and recurrence, but this is not accessible to all patients. Hence, new treatments are required to address these chronic wounds. One possible adjuvant treatment for VLU is human decellularised dermis (DCD), a type of skin graft derived from skin from deceased tissue donors. Although DCD has the potential to promote ulcer healing, there is a paucity of data for its use in patients with VLU.
This is a multicentre, parallel group, pragmatic randomised controlled trial. One hundred and ninety-six patients with VLU will be randomly assigned to receive either the DCD allograft in addition to standard care or standard care alone. The primary outcome is the proportion of participants with a healed index ulcer at 12 weeks post-randomisation in each treatment arm. Secondary outcomes include the time to index ulcer healing and the proportion of participants with a healed index ulcer at 12 months. Changes in quality of life scores and cost-effectiveness will also be assessed. All analyses will be carried out on an intention-to-treat (ITT) basis. A mixed-effects, logistic regression on the outcome of the proportion of those with the index ulcer healed at 12 weeks will be performed. Secondary outcomes will be assessed using various statistical models appropriate to the distribution and nature of these outcomes.
Ethical approval was granted by the Bloomsbury Research Ethics Committee (19/LO/1271). Findings will be published in a peer-reviewed journal and presented at national and international conferences.
ISRCTN21541209.
ISRCTN21541209.The aim of this study was to evaluate the association between integrated care and health-related quality of life (HRQOL) in a primary care practice population.
A cross-sectional survey study.
Primary care practice population.
A sample (n=5562) of patients in two general practitioner practices in the Netherlands.
The Rainbow Model of Integrated Care Measurement Tool patient version and EQ-5D was used to assess integrated service delivery and HRQOL. The association between integrated care and HRQOL groups was analysed using multivariate logistic regression.
Overall, 933 respondents with a mean age of 62 participated (20% response rate) in this study. The multivariate analysis revealed that positive organisational coordination experiences were linked to better HRQOL (OR=1.87, 95%?CI 1.18 to 2.95), and less anxiety and depression problems (OR=0.36, 95%?CI 0.20 to 0.63). Unemployment was associated with a poor HRQOL (OR=0.15, 95%?CI 0.08 to 0.28). Ageing was associated with more mobility (OR=1.06, 95%?ies are positively associated with HROQL of adult patients in a primary care context, adding to the evidence of an association between integrated care and HRQOL. Also, unemployment, ageing and being female are accumulating risk factors that should be considered when designing integrated primary care programmes. Further research is needed to explore how various integration types relate to HRQOL for people in local communities.The prevalence of at-risk drinking is far higher among those in contact with the criminal justice system (73%) than the general population (35%). However, there is little evidence on the effectiveness of alcohol brief interventions (ABIs) in reducing risky drinking among those in the criminal justice system, including the prison system and, in particular, those on remand. Building on earlier work, A two-arm parallel group individually randomised Prison Pilot study of a male Remand Alcohol Intervention for Self-efficacy Enhancement (APPRAISE) is a pilot study designed to assess the feasibility and acceptability of an ABI, delivered to male prisoners on remand. https://www.selleckchem.com/products/cy-09.html The findings of APPRAISE should provide the information required to design a future definitive randomised controlled trial (RCT).
APPRAISE will use mixed methods, with two linked phases, across two prisons in the UK, recruiting 180 adult men on remand 90 from Scotland and 90 from England. Phase I will involve a two-arm, parallel-group, individually rough meetings and events.
ISRCTN27417180.
ISRCTN27417180.Harnessing the immune system to treat cancer through inhibitors of CTLA4 and PD-L1 has revolutionized the landscape of cancer. Rational combination strategies aim to enhance the antitumor effects of immunotherapies, but require a deep understanding of the mechanistic underpinnings of the immune system and robust preclinical and clinical drug development strategies. We review the current approved immunotherapy combinations, before discussing promising combinatorial approaches in clinical trials and detailing innovative preclinical model systems being used to develop rational combinations. We also discuss the promise of high-order immunotherapy combinations, as well as novel biomarker and combinatorial trial strategies. SIGNIFICANCE Although immune-checkpoint inhibitors are approved as dual checkpoint strategies, and in combination with cytotoxic chemotherapy and angiogenesis inhibitors for multiple cancers, patient benefit remains limited. Innovative approaches are required to guide the development of novel immunotherapy combinations, ranging from improvements in preclinical tumor model systems to biomarker-driven trial strategies.Disruption of splicing patterns due to mutations of genes coding splicing factors in tumors represents a potential source of tumor neo-antigens, which would be both public (shared between patients) and tumor-specific (not expressed in normal tissues). In this study, we show that mutations of the splicing factor SF3B1 in uveal melanoma (UM) generate such immunogenic neo-antigens. Memory CD8+ T cells specific for these neo-antigens are preferentially found in 20% of UM patients bearing SF3B1 mutated tumors. Single cell analyses of neo-epitope specific T cells from the blood identified large clonal T cell expansions, with distinct effector transcription patterns. Some of these expanded TCRs are also present in the corresponding tumors. CD8+ T cell clones specific for the neo-epitopes specifically recognize and kill SF3B1-mutated tumor cells, supporting the use of this new family of neo-antigens as therapeutic targets.